Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Apr 13;4(2):205-221.
doi: 10.1016/j.jcmgh.2017.04.001. eCollection 2017 Sep.

Colonic Microbiota Encroachment Correlates With Dysglycemia in Humans

Affiliations
Free PMC article

Colonic Microbiota Encroachment Correlates With Dysglycemia in Humans

Benoit Chassaing et al. Cell Mol Gastroenterol Hepatol. .
Free PMC article

Abstract

Background and aims: Mucoid structures that coat the epithelium play an essential role in keeping the intestinal microbiota at a safe distance from host cells. Encroachment of bacteria into the normally almost-sterile inner mucus layer has been observed in inflammatory bowel disease and in mouse models of colitis. Moreover, such microbiota encroachment has also been observed in mouse models of metabolic syndrome, which are associated low-grade intestinal inflammation. Hence, we investigated if microbiota encroachment might correlate with indices of metabolic syndrome in humans.

Methods: Confocal microscopy was used to measure bacterial-epithelial distance of the closest bacteria per high-powered field in colonic biopsies of all willing participants undergoing cancer screening colonoscopies.

Results: We observed that, among all subjects, bacterial-epithelial distance was inversely correlated with body mass index, fasting glucose levels, and hemoglobin A1C. However, this correlation was driven by dysglycemic subjects, irrespective of body mass index, whereas the difference in bacterial-epithelial distance between obese and nonobese subjects was eliminated by removal of dysglycemic subjects.

Conclusions: We conclude that microbiota encroachment is a feature of insulin resistance-associated dysglycemia in humans.

Keywords: BMI, body mass index; HPF, high-powered field; IBD, inflammatory bowel disease; Metabolic Syndrome; Microbiota; Mucus Layer; PBS, phosphate-buffered saline; TLR, Toll-like receptor.

Figures

None
Figure 1
Figure 1
Microbiota localization in human with or without metabolic syndrome. Colonic biopsies were collected during colonoscopy procedure and placed in methanol-Carnoy fixative solution. Representative images of confocal microscopy analysis of microbiota localization; Muc2 (green), actin (purple), bacteria (red), and DNA (blue). (A) Patients without diabetes mellitus. (B) Patients with diabetes mellitus. Bar = 10 μm; n = 42. HbA1C, hemoglobin A1C.
Figure 2
Figure 2
Metabolic syndrome correlates with microbiota encroachment in human. Colonic biopsies were collected during colonoscopy procedure and placed in methanol-Carnoy fixative solution, followed by confocal microscopy analysis of microbiota localization. (A) Distances of the closest bacteria to intestinal epithelial cells was measured in 5 high-powered fields per sample and plotted versus fasting blood glucose concentration. (B) Distances of the closest bacteria to intestinal epithelial cells was measured in 5 high-powered fields per sample and plotted versus hemoglobin A1C level. (C) Distances of the closest bacteria to intestinal epithelial cells was measured in 5 high-powered fields per sample and plotted versus body mass index. (D–G) Distances of the closest bacteria to intestinal epithelial cells per condition over 5 high-powered field according to the diabetes mellitus (D, E) or the obese (F, G) status. In E, obese patients were removed from the analysis. In G, patients with diabetes mellitus were removed from the analysis. Linear regression line was plotted and R2 and P values were determined. Significance was determined by Student t test. *P < .05); n = 42; red dots represent subjects with diabetes. HbA1C, hemoglobin A1C; IEC, intestinal epithelial cells.
Figure 3
Figure 3
Circulating lipid profile does not correlate with microbiota encroachment in human. Colonic biopsies were collected during colonoscopy procedure and placed in methanol-Carnoy fixative solution, followed by confocal microscopy analysis of microbiota localization. (A) Distances of the closest bacteria to intestinal epithelial cells was measured in 5 high-powered fields per sample and plotted versus cholesterol concentration. Linear regression line was plotted and R2 and P values were determined. (B) Distances of the closest bacteria to intestinal epithelial cells was measured in 5 high-powered fields per sample and plotted versus triglyceride concentration. Linear regression line was plotted and R2 and P values were determined. (C) Distances of the closest bacteria to intestinal epithelial cells was measured in 5 high-powered fields per sample and plotted versus low-density lipoprotein concentration. Linear regression line was plotted and R2 and P values were determined. n = 42; red dots represent subjects with diabetes. IEC, intestinal epithelial cells; LDL, low-density lipoprotein.
Figure 4
Figure 4
Dysglycemia correlates with microbiota encroachment in human with diabetes. Colonic biopsies were collected during colonoscopy procedure and placed in methanol-Carnoy fixative solution, followed by confocal microscopy analysis of microbiota localization. Distances of the closest bacteria to intestinal epithelial cells was measured in 5 high-powered fields per sample and plotted versus hemoglobin A1C level (A, B), fasting blood glucose concentration (C, D), or body mass index (E, F). Linear regression line was plotted and R2 and P values were determined. n = 42; red dots represent subjects with diabetes (AC, and E) or obese subjects (B, D, and F). HbA1C, hemoglobin A1C; IEC, intestinal epithelial cells.
Figure 5
Figure 5
Ethnicity or antibiotic use do not correlate with microbiota encroachment in human. Colonic biopsies were collected during colonoscopy procedure and placed in methanol-Carnoy fixative solution, followed by confocal microscopy analysis of microbiota localization. (A) Distances of the closest bacteria to intestinal epithelial cells per condition over 5 high-powered fields according to the ethnicity. (B) Distances of the closest bacteria to intestinal epithelial cells per condition over 5 high-powered fields according to the antibiotic use status. IEC, intestinal epithelial cells.
Figure 6
Figure 6
Antidiabetic drug use does not impact microbiota encroachment in human. Colonic biopsies were collected during colonoscopy procedure and placed in methanol-Carnoy fixative solution, followed by confocal microscopy analysis of microbiota localization. (A) Distances of the closest bacteria to intestinal epithelial cells was measured in 5 high-powered fields per sample and plotted versus hemoglobin A1C level. Linear regression line was plotted and R2 and P values were determined. (B) Patients using metformin drug were removed from the analysis. (C) Patients using insulin drug were removed from the analysis. (D) Patients using glipizide drug were removed from the analysis. Linear regression line was plotted and R2 and P values were determined. n = 42; red dots represent subjects with diabetes. HbA1C, hemoglobin A1C; IEC, intestinal epithelial cells.
Figure 7
Figure 7
Metabolic syndrome correlates with increased CD19+cell population in the intestinal mucosa. Colonic biopsies were collected during colonoscopy procedure and placed in methanol-Carnoy fixative solution. Representative images of confocal microscopy analysis of CD19 (A) and CD68 (C) staining (green) and DNA (blue). Number of CD19+ (B) and CD68+ (D) cells per field (0.102 mm2). Significance was determined by Student t test. *P < .05). Bar = 50 μm; n = 7.
Figure 8
Figure 8
Streptozotocin-induced type 1 diabetes and associated increased fecal glucose is not sufficient to induce microbiota encroachment in mice. Type 1 diabetes was induced in mice by streptozotocin injection for 5 consecutive days. (A) Body weight over time. (B) Five-hour fasting blood glucose concentration on Day 0 and Day 15. (C) Day 0 and Day 15 fecal glucose concentration. (D) Representative images of confocal microscopy analysis of microbiota localization; Muc2 (green), actin (purple), bacteria (red), and DNA (blue). (E) Distances of the closest bacteria to intestinal epithelial cells per condition over 5 high-powered fields according to the diabetes mellitus status. Significance was determined by Student t test (*P < .05). Bar = 50 μm; n = 5–9. IEC, intestinal epithelial cells; STZ, streptozotocin.

Similar articles

See all similar articles

Cited by 20 articles

See all "Cited by" articles

References

    1. Hooper L.V., Macpherson A.J. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol. 2010;10:159–169. - PubMed
    1. Chassaing B., Darfeuille-Michaud A. The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology. 2011;140:1720–1728. - PubMed
    1. Xavier R.J., Podolsky D.K. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–434. - PubMed
    1. Frank D.N., St Amand A.L., Feldman R.A., Boedeker E.C., Harpaz N., Pace N.R. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007;104:13780–13785. - PMC - PubMed
    1. Gevers D., Kugathasan S., Denson L.A., Vazquez-Baeza Y., Van Treuren W., Ren B. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe. 2014;15:382–392. - PMC - PubMed

LinkOut - more resources

Feedback